Posted
by
samzenpus
on Thursday April 04, 2013 @11:33PM
from the you-re-arrange-me-till-I'm-sane dept.

An anonymous reader writes "The prelimbic region of the prefrontal cortex in the human brain is thought to play a key role in drug addiction, and researchers at the National Institute on Drug Abuse wanted to see if manipulating cells there had a positive or negative impact on that addiction. They got some rats addicted to cocaine but not before loading them up with light sensitive proteins called rhodopsins that were placed in their prefrontal cortex, attaching to the neurons there. By shining a tuned laser light on to the prefrontal cortex, it was possible to activate and deactivate the cells. By turning them on with the laser, the addictive behavior of the rats was removed. Turning them off, even in non-addicted rats, saw the addictive behavior return or introduced."

Just looked at the paper and...Where is the scatter plot between lever presses and cocaine infusions??? NATURE EDITORS, DEMAND TO SEE THE ACTUAL DATA AND NOT JUST AVERAGES. Put it in the supplements if it is too complicated for the normal audience.

While I don't have fewer digits than you, I do have a hell of a lot smaller number.I think the GP is right, although I haven't done a real study, either. Then there used to be reasoned scientific debates and discussions in just just about every story. Sure, there were troll posts, oft repeated memes about Natalie Portman and hot grits, but now we just get goatse, MyCleanPC spam, and stupid, rambling shit by apk that goes on for pages of unintelligible, psychotic nonsense.

Redundant is appropriate, by definition the raw data is redundant after it has been properly analyzed, by definition a published paper is a "proper" analysis. It may be wrong but if it's the only analysis then by definition it is the best analysis we have. Einstein's famous 1905 paper was 3 pages long and had zero references, it was quickly recognized as a work of uncommon genius by other physicists.

The first thing they teach you in statistics is to create a scatter plot and just eyeball it for a one of several standard curves that MIGHT fit, the next step is averages (or some other metric) to see if your guess holds up to scrutiny.
Thing is, eye-balling is not evidence and publishing only the calculated curve is normal practice. I don't have a Nature account so I can't easily confirm/deny the AC's claim that the raw data is unavailable (ironically because the AC did not publish his raw data). However since this looks like government funded research I think it's more likely the AC just eye-balled the paper and missed it.

Besides all that, a real scientist wouldn't bitch and moan if they couldn't find the raw data, they would just contact the author and ask politely, if that didn't work they would run their own experiments. At the end of the day the scientific way to overturn the results from one experiment is run one or more independent experiments that convincingly refute the original results.

To paraphrase one of the best science teachers to ever walk the earth - "The key to science is that if your beautifully presented, leather bound, iron-clad logic disagrees with experiments, it's wrong". - Feynman [youtube.com]

A comment on your post, if you have the stats ability & tools, it's fun & quick to check the raw data.Certainly cheaper and faster than trying to reproduce the experimental data.I've found a few problems with the data, and/or in the analysis in my time; most are due to simple ignorance, (not all 'real scientists' *gasp* are stats experts), or falling into the trap of 'finding what you are looking for'.Granted peer review is supposed to catch this, but I wonder how many g

The original article clearly was not read. These rats had their genome changed to have more rhodopsins in their prefrontal cortex. This will not happen with humans in advance of any drug addiction issues (it would have to be done with the sperm/egg?). tldr; not going to happen.

Electroconvulsive therapy is broad, and even its most targeted implemented sends electricity to places it doesn't need to go. It must also pass through tissues that have no therapeutic reason to be exposed to electric current.

An internally-mounted system could be far more precise; possibly even as good as this experiment.

The best analogy I can come up with is: ECT is like trying to chisel a sculpture with a jackhammer.

Electroconvulsive therapy is the mental / medical equivilent of pounding on the TV to "fix" it, and is a last ditch treatment used when the simptoms cannot be treated any other way.

It, as the name implies, creates a seizure in the paitent by applying voltages across rather wide areas of the brain. Originally uncontrolled voltages (because it came through skin, bone, etc) into, nearly random brain tissues (because it was applied in ignorance, through multiple barriers, with no gu

Gene therapy is just hard in general. The exact effect of a virus is unpredictable, it'll only alter a small number of cells at best and will likely kill a lot more in the attempt, or turn them cancerous. It isn't even out of clinical trial yet. The blood-brain barrier shouldn't pose any difficulty though: Simply inject directly into CSF and bypass it entirely.

Gene therapy is not particularly hard, and there's clinical trials and decades old cases where it have had success. Why is this myth propagated?Did the major fuckup and misconduct in the Jesse Gelsinger case really have that much publicity?

Though I guess, every religious nut, moral-code internet warrior, environmentalist nutcase and anti-GMO opinionist would of course latch onto this outlier case and present it as a rule rather than exception, because some delusion of purity is more important than saving an

Gene therapy is not particularly hard, and there's clinical trials and decades old cases where it have had success. Why is this myth propagated?
Did the major fuckup and misconduct in the Jesse Gelsinger case really have that much publicity?

Though I guess, every religious nut, moral-code internet warrior, environmentalist nutcase and anti-GMO opinionist would of course latch onto this outlier case and present it as a rule rather than exception, because some delusion of purity is more important than saving and improving lives.

Disclaimer: I work in neuroscience and have used viral transfection quite a lot.

Myth? It's not trivial to get the infectous titer and purity of the virus right and it's even harder (read: almost impossible) to predict the exact expression levels that the virus will cause in an actual brain. Much less if such a potential overexpression of a non-native protein will mess up regular cell trafficking/function. Even if the protein is thought to be harmless (as is the case with Channelrhodopsin or Halorhodopsin), the sheer fact that the cell now has to produce, store and process large numbers of something it usually doesn't have can cause problems and take resources away from the normal function. Plus any virus that will stably integrate into the genome can cause all kinds of fuck up down the road since you don't know WHERE it will integrate and what other function it might overwrite.

Don't get me wrong, it is interesting, it is potentially very beneficial but I'd still be cautious when applying it in the brain (as opposed to applying it in muscle or skin cells) since adult neurogenesis isn't really happening much...

Adult myogenesis in skeletal muscles isn't really happening much either.As for integration into the genome, I was under the impression that you can actually chose the place in the genome it would integrate in, but that this is mostly irrelevant as adenoviral vectors are preferred over lentiviral ones.

Adult myogenesis in skeletal muscles isn't really happening much either.
As for integration into the genome, I was under the impression that you can actually chose the place in the genome it would integrate in, but that this is mostly irrelevant as adenoviral vectors are preferred over lentiviral ones.

True, but I would say that a few lost muscle cells are less problematic than a few neurons lost in the wrong part of the brain. AFAIK there is no reliable way to control the site of lentiviral integration. Plus, purifying lenti properly is nasty, the stuff can be either quite neurotoxic or not infectious at all if something goes wrong during that step.
Recombinant Adeno Associated Virus is much less problematic, it's dead simple to manufacture and only the potential protein overload problem remains (and in

so what you are saying is that it has the potential to turn out like resident evil?

No, I was thinking of something still lethal but less freaky: cancer. Plus, even if one of the patients goes insane for whatever strange one-in-a-billion chance, it's not really infectious unless he's still capable of drilling a hole into your skull and injecting a tiny amount of purified virus into precisely the correct area of the brain (think micrometer precision). So no zombie apocalypse there, sorry.

Yes but it's mandatory to add the tag "may cure drug addiction" - or some other socially useful claim - to any research involving the brain. That way you get media coverage and a better chance of funding.

re: cocaine was a terrible example since it really is not addictive to begin with.. [emphasis mine].
Dude! You think cocaine is not addictive? You're completely wrong.
It is addictive because of its effect on the mesolimbic reward pathway. I link you to wikipedia's article on cocaine [wikipedia.org] because the medical articles I found are behind paywalls and you might not be able to get to them unless you're on a university network that has medical journal access like UCSD does:

So you are saying that cocaine is addictive the same way sex is addictive? You are an idiot. Stop spreading war on drug FUD.

I don't know if I would be classified as an addict, but I used blow on the every weekend and occasionally to get by at work for about 5 years. I moved cities after a nasty breakup and had to go cold turkey on both. I missed the sex more than the coke. The war on drugs is a sham.

Considering how sex is one of the few things that can motivate even animals to kill their own kind for "no good reason" (i.e. neither food nor defense of their own life), I'd say that sex is one pretty powerful motivator.

It would be interesting to see whether animals would also kill each other to get another load of some drug after you get them addicted.

Sex is a hugely powerful motivator but few higher species will kill each other for mating. Most will carefully regulate their "fighting" to be mostly display and instinctively know when they are outmatched and stop aggression and retreat. It is not in the species' best interest for lots of their own kind to die in such activities.

You're not captain obvious, you're captain misunderstanding-the-whole-fucking-concept.The laser doesn't destroy any chemical reaction. It simply excites neurons that have a regulatory effect on addiction, the same effect could likely be had with electrode stimulation, or transcranial magnetic stimulation, only that the optogenetic approach have much better targeting resolution and neuron selectivity.

"I don't know where you get your delusions, laser brain." - Leia
Well, now we know Han was trying to kick and lasers were his methadone... And, from the footer on/. right now..
"It's easier to take it apart than to put it back together. -- Washlesky"

We may never know! It all depends on who sets the NIH funding agenda and who has deep pockets. Cocaine addiction seems to be the primary focus of most addiction research, presumably because the effect is so sudden and there's no one to lobby against its prohibition.

It's more than just the political reasons. Cocaine is a pretty direct and uncomplicated way to manipulate a dopamine pathway like the reward system.Heroin and alcohol have more complex modes of action to hit the reward system. When you're still trying to work out the pathway and its dynamics you want to avoid complicating effects.

Unfortunately, I say the answer is quite likely yes, and probably better than it would treat drug addiction.
Unfortunately, as people aren't rats — and probably the best thing I took away from rehab — you don't have a drug problem, you have drug solution to your person problems. People use drugs to turn off their shitty lives. Of course, drugs lead to shitty lives and the cycle continues, but fixing the "I'm not addicted to drug X" problem won't fix the fact that people relapse after years and y

That's because there isn't much of an altered-state "high" with nicotine or caffeine. Although they can be addictive (especially nicotine), being "on" them doesn't really alter perception, warp senses, and severely impair judgement, memory, motor skills, productivity, cognition, etc, like being high on alcohol, cocaine, heroine, marijuana, meth, LSD, PCP, etc.

Let's take heroin addiction for example. You know how many heroin addicts that get clean, yet go back to using the heroin? Pretty much all of them. Turning off the "addictive" cell won't change that. It's not about the addiction, it's about the high. It's about how the drug makes you feel.

They're not turning off anything, actually; they're restoring normal function that's destroyed by the addiction. This is the sort of stuff that stays behind after recovery and that makes it easy to relapse. The behavioural studies they performed more-or-less modelled the situation you describe: the researchers found that after four doses of cocaine, rats would normally ignore electric shocks in order to get at the drug. After treatment, the rats became less obsessed with the high and would not risk getting electrocuted again in order to have it. It wasn't as much of a return to normal function as a rat that had only had cocaine once, but it took a while to return to full addict behaviour.

So, yes, it does address the functional problem that normal rehab fails to remedy. The area they chose to stimulate was specifically implicated as being responsible for loss of control in addicts.

No, they go back because it alleviates serious pain from major mental illness, which the vast majority of addicts have. By "major mental illness" I don't mean just garden-variety depression or anxiety, but disorders that cause wild mood swings to enraged/suicidal/terrified out of the blue, scary hallucinations, and so forth. They also don't develop coping skills for daily life, so the problems we quickly deal with & move beyond accumulate for them until they can reach their method of coping (e.g. the

> Let's take heroin addiction for example. You know how many heroin addicts that get clean, yet go back to using the heroin? Pretty much all of them. Turning off the "addictive" cell won't change that. It's not about the addiction, it's about the high. It's about how the drug makes you feel.

Ok, feel a need to state the obvious.

Feeling the high won't destroy your life. Feeling a constant need for getting high (addiction) will destroy your life.Many drugs are actually beneficial if used wisely. Same as eve

>"Feeling the high won't destroy your life. Feeling a constant need for getting high (addiction) will destroy your life."

Actually, for mind/reality-altering drugs (which excludes caffeine, nicotine, sugar, etc) the actual high *can* contribute to destroying lives. While high, judgement and functionality are so severely impaired that there is a huge risk of injury to one self and to others. And all the while, the person is completely unproductive- can't work, can't learn, can't do much of anything usef

>"Feeling the high won't destroy your life. Feeling a constant need for getting high (addiction) will destroy your life."

Actually, for mind/reality-altering drugs (which excludes caffeine, nicotine, sugar, etc) the actual high *can* contribute to destroying lives. While high, judgement and functionality are so severely impaired that there is a huge risk of injury to one self and to others. And all the while, the person is completely unproductive- can't work, can't learn, can't do much of anything useful to society or for themselves.

So yes, the need for getting high does contribute to "destroying your life", and can be the longest part of the destruction, the actual high contributes too.

Sorry, this is total bullshit. For example, let's look at opiate drugs like heroin, which all act similarly upon the brain. It has been shown that as long as the opiate addict has a steady high-quality supply of the drug, very little in the way of harm occurs either physically or mentally. There are many famous historic examples of high-functioning opium addicts, the poet Coleridge is perhaps the best known example. More importantly, and more recently, experiments in Switzerland and elsewhere have demonstra

Yes, there can be high-functioning drug addicts with many drugs, especially opiates as you pointed out. It can vary greatly depending on the drug and how it is used. I didn't mean to imply it is not possible, just that there are, indeed, many cases where the high *is* a problem for the user and society, not just the seeking of it. A quick look at drunk driving or productivity/reasoning while on pot will show that. And I am not sure there is any high-functi

Crazy they called me! CRAZY! But it is not _I_ who have surrendered the war on drugs! I know drugs - and the only real cure is PAIN. And the best PAIN? Direct laser to the brain!

Now, I know what you're all thinking! Dr. Madd, you're thinking, the brain doesn't have any pain receptors! You're thinking I just want to cure addiction with death! Ha! Death is no cure - it is FAILURE.

For you see - this is not some fleshy-burny laser, oh no! This is a laser set to trigger two particular threshold states in the neurotransmitter pathways... specifically, the pathways relating to heat, and cold.

And as any CHILD knows, both of those combined equate to the sensation of PAIN. Raw, sweet PAIN - far sweeter than any drug. Such an all-encompassing PAIN.

Such ecstasy an horror is unleashed, that the mind scrambles through everything it can, just to make sense of it. The end result is usually one of two things - a hyper-receptive state, where the... subject is willing to accept instruction in thanks for the experience, or a simple silence that at least commits no more crimes such as seeking out drugs.

Such a cure! Were I a less modest man, I would call it a REVOLUTION in treatment!

I expect to be able to roll out full production within the next two to five years, and am highly interested in investments.

Better still, just pick up some homeless drug addicts from the streets, inject their brains with genetically engineered chemicals and fire electromagnetic radiation at them. This would represent enormous savings in medical care for drug addicts, and the best part is, the more you do it.. the more you save!

Time for the medical industry to get a bill drafted.. call it the "Cocaine User National Treatment of Substances" act. The genetically engineered chemical* would be far cheaper than the combined med

So now there's a medical use for those frickin' sharks with laser beams! The only confound while doing the longitudinal study will be whether the rats were scared straight from addiction by the laser beam or by being confronted by the shark in the first place. So an extra experiment will have to be done using sharks that do not have laser beam capabilities.;>)
Now the only problem is in getting the tiny little scuba suits for the rats, or the very large land-shark suits for the sharks (that have the ap

This opens an opportunity for corporations to fund this research and eventually monetize it. According to TFA, they can induce addictive behavior in previously unaddicted rats with the combination of rhodopsins and lasers. All they have to do is extend the technique to work with television illumination. Then they can load up processed food with the rhodopsin and get viewers addicted to anything they put in their mouths.

Think about nicotine style consumer addition on things that are normal and legal. Genus!

Moving from NYC to Shanghai cured my taste for blow. First month here kinda sucked but not s bad as getting my skull open and having lasers pointed at my neocortex.

Genetic engineering and laser is not how we end this problem. End the "war on Drugs," end the "war on Terror". Use the trillions saved to educate people and provide rehab. Our economy would be stronger, schools better, streets safer, and Mexico could get regain control from the vicious drug cartels.

Laser shots to the brain for addicts are a case of applying too much technology. Even a Colt 45 is a waste of effort. It is my thought that a guillotine can repair a lot of jerks and do so with almost no investment or maintenance at all.. It doesn't even need to be sharp if the blade is heavy enough. Then again a sledge hammer is even simpler. It is a cure. It is inexpensive. It solves a social nightmare. It is an object that inspires others to reform. And if we ever get smart enough we could compost

Caffeine dependence goes away after a week or so. Many people are so tolerant of caffeine that the stimulant doesn't give them much more energy than they'd normally have in a day; it's just that you get it more rapidly and can control when it's available.

What happened here is that the animals were put under stress, and tried to develop some kind of behaviour they hoped would result in the stress to go away. From their point of view, it "worked". It's self conditioning, not "pointless".

Quite the opposite, from the pigeons' point of view, what they did made the food appear. They tried to appease their "god" if you want, so he would give them food.